2023 Author: Bryan Walter | [email protected]. Last modified: 2023-05-21 22:24
Rat somatosensory cortex
Researchers at the University of California, Los Angeles have found that mice with fragile X syndrome exhibit the same neurological symptom as many autistic patients - tactile hypersensitivity. It turned out that hypersensitivity is based on the inability of neurons in the somatosensory cortex to adapt to repetitive stimuli. The research is published in The Journal of Neuroscience.
Autism spectrum disorders are known to be inherited, but the genetics of this group of diseases are very complex. It is believed that genetic factors contribute to the risk of developing the disease in more than half of cases. Most often, the disease is multifactorial in nature, but in rare cases it is caused by a mutation in one gene. An example of a monogenic disorder associated with autism is fragile X syndrome, which accounts for about two percent of autistic disorders.
In fragile X syndrome, FMR1 gene expression is disrupted as a result of the accumulation of trinucleotide repeats at the gene locus. The protein encoded by the FMR1 gene is required for the formation of contacts between neurons, and, accordingly, for the development of the nervous system. Geneticists have developed a line of mice with fragile X-chromosome syndrome, in which the FMR1 gene is "turned off". This line is one of the models for the study of autism.
Autistic patients often exhibit sensory hypersensitivity, that is, heightened perception of various external stimuli. For example, tactile hypersensitivity is manifested in the fact that people are sensitive to touch. In their study, neuroscientists found that the same is observed in the aforementioned FMR1 knockout mice. It turned out that such mice much more often than control ones showed an avoidance response in response to stimulation of antennae (vibrissae).
To explain tactile hypersensitivity, the scientists put forward three hypotheses, implying a change in the normal activation of neurons in the somatosensory cortex of experimental mice. The cause of hypersensitivity could be either hyperexcitation of neurons in response to a stimulus, or an increase in the number of neurons involved in the reaction, or an inability to adapt to repetitive stimuli.
To find out which hypothesis is correct, a genetically encoded fluorescent calcium sensor was introduced into the mice in the brain, which makes it possible to track the activation of individual neurons. Thus, the researchers observed a response in response to stimulation of the antennae at the level of individual neurons through a hole in the skull of a fixed but living mouse. In the experiment, data was collected on the result of twenty touches.
Schematic diagram of an experiment to visualize the response of neurons in the brain of mice (left) and individual excited neurons (right)
The number and intensity of excitation of individual neurons in response to touch in hypersensitive mice did not change. Normally, when exposed to several repetitive stimuli, the excitation of neurons begins to decrease in response to each subsequent stimulus. However, the neurons of the studied mice were unable to adapt to repeated touches - neither in two-week-old nor in adult animals. Apparently, it was the inability to reduce arousal in response to repetitive stimulus that caused the tactile hypersensitivity of the mice. The authors of the work note that previously, defects in neural adaptation were also seen in autistic children in a study using magnetic resonance imaging.
Elucidating the mechanism of sensory hypersensitivity is an important step in the study of the nature of autism, because hypersensitivity, according to the authors of the work, underlies many of the symptoms of autism in humans, such as hyperexcitation, decreased attention and seizures.
In addition to the fragile X syndrome, several other single mutations are known that lead to the development of autism symptoms. For example, this is a deletion or duplication of a site on the sixteenth human chromosome. Many of these mutations also exist in mouse models.
